Abstract P5-11-05: Overexpression of girdin in nucleus indicates poor disease-free survival in ER-positive breast cancer

Abstract

Abstract Background Girdin is identified as a novel modulator of the PI3K-Akt signaling pathway in regulating neurons integration during neurogenesis process. Recently, several studies demonstrated that Girdin and its phosphorylation type (p-Girdin) were also involved in tumor metastasis and angiogenesis. However, the clinical implications of Girdin and p-Girdin in breast cancer remain unclear. In this study, we detected the expression pattern of p-Girdin (Ser1416) and Girdin in breast cancer to uncover the association between p-Girdin/Girdin status and clinicopathological parameters like estrogen receptor (ER), progestogen receptor (PR), and human epidermal growth factor receptor 2 (Her2), etc. Methods This study included 250 patients who were histologically confirmed as invasive ductal breast cancer and underwent mastectomy in the Department of Breast Surgery in Shanghai Cancer Center during 2001 to 2006. We performed immunohistochemistry of p-Girdin/Girdin on tissue microarrays constructed from above specimens. Results We observed that Girdin was mainly located in the cytoplasm of mammary epithelial carcinoma cells (195/248, 78.63%) while p-Girdin was mainly located in the nucleus (160/250, 64.00%). However, Girdin/p-Girdin was also weakly expressed in the nucleus/cytoplasm (77/248, 31.05% for Girdin and 193/250, 77.2% for p-Girdin). By the Chi-square test, we found that Girdin in the nucleus (GN) was positively associated with ER status (P = 0.012); Girdin in the cytoplasm (GC) was positively associated with ER (P = 0.004), PR (P = 0.028), and Her2 status (P = 0.004); p-Girdin in the cytoplasm (pGC) was positively associated with PR status (P = 0.001) and negatively associated with tumor size (P = 0.025). However, no significant association was observed between p-Girdin in the nucleus (pGN) and other parameters. Using Kaplan-Meier method, we disclosed a trend that GN indicated poor disease-free survival (DFS) in ER-positive breast cancer (P = 0.075). After adjusted for histological grade and tumor size, multivariate cox regression analysis confirmed this trend (HR = 3.051, 95% CI: 1.137-8.191, P = 0.027). Furthermore, GC was prone to associating with poor DFS, especially in stage II (P = 0.079) and grade III (P = 0.058) patients. Conclusions Our work reveals, for the first time, that the location and expression pattern of both Girdin and p-Girdin (Ser1416) in breast cancer, suggesting that p-Girdin/Girdin are associated with ER, PR and Her2 status. In addition, Girdin in the nucleus is associated with poor DFS in ER-positive breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-11-05.